Stroke is a leading cause of disability, with an estimated 795,000 cases reported in the US each year. As many as 70% of patients who suffer a stroke display a long-term impairment in upper extremity motor function. Many stroke patients exhibit associated risk factors which can impair recovery of function, such as advanced age. The development of rehabilitative strategies to improve the recovery of motor function in the context of advanced age is of key importance. We propose to evaluate a novel early stage therapy to improve stroke recovery which utilizes stimulation of the vagus nerve paired with rehabilitative training. Pairing vagus nerve stimulation (VNS) with movement results in highly specific, long-lasting neuroplasticity in rat primary motor cortex. Furthermore, VNS delivered during rehabilitation improves recovery of forelimb speed and strength after an ischemic lesion of the motor cortex in young adult rats. To evaluate if VNS paired with physical rehabilitation may be useful in stroke patients, we propose to test the therapy in a model that more accurately represents the clinical population. Because advanced age is a leading risk factor for stroke and may limit plasticity, the experiments described in this proposal will evaluate VNS in a model of stroke at an advanced age. The first aim of the study will assess the ability of VNS paired with rehabilitative training to improve recovery of motor function after ischemic stroke in aged rats. The second aim of this proposal will examine structural plasticity mechanisms that underlie recovery after stroke. The third aim of the study will assess the ability of VNS paired with physical training to enhance map plasticity in motor cortex of aged rats. We hypothesize that in aged rats, VNS paired with physical training will result in improved recovery of function, increased structural plasticity, and enhanced map plasticity beyond physical training alone. The results of the proposed experiments will clarify the relationship between advanced age and recovery of motor function are stroke. Insights from these studies will help to delineate the clinical population for which VNS paired with physical rehabilitation is likely to confer therapeutc benefits and improve the likelihood of successful translation of the therapy.